This research deals with the isolation and synthesis of antiglaucoma compounds, primarily derived from Cannabis sativa. It is well established that the lipophilic cannabinoids can lower intraocular pressure (IOP) and thus may be useful in the treatment of glaucoma. Recently reported work, supported by preliminary work in our laboratories has shown that there are water soluble components in Cannabis that lower IOP. Our results have demonstrated that the fall in IOP in rabbits, caused by water soluble components from Cannabis was as large as 60% and lasted for up to 72 h from a single intravenous injection! This is the maximum fall possible since the IOP was reduced to the episcleral venous pressure. The active compounds responsible for the IOP fall will be isolated by the use of high performance liquid chromatography (HPLC) and droplet countercurrent chromatography (DCC). The progress of all isolation procedures will be monitored by testing for IOP lowering activity in rabbits. Once the active compound(s) have been isolated in pure form, their chemical structures will be determined primarily by spectroscopic means such as 1H and 13C NMR, IR, UV, MS, and where applicable single crystal X-ray crystallography. If warranted, large quantities of active compound(s) will be isolated for further testing. Structure activity relationships for these compounds will be studied by synthesis and screening of analogs and known compounds of similar structure. We also plan to synthesize water soluble derivatives, using established methodology, of naturally occurring cannibinoids. We will attempt to develop a drug that is easily delivered to the eye and causes no psychoactivity. Lastly, we plan on screening other plants for IOP lowering activity. Selection of plants will be guided by the structural types isolated from Cannabis.